Effect of phenotypic presentation on survival in ALS-FTD

Abstract

Within the Amyotrophic Lateral Sclerosis (ALS)–Frontotemporal dementia (FTD) spectrum there is much heterogeneity in survival. The current study aimed to examine how initial symptoms: motor versus cognitive affected survival, the cognitive/ behavioural profile between ALS- FTD and bvFTD and how brain atrophy patterns differ. The cognitive and behavioural profile was examined 55 ALS-FTD and 40 bvFTD patients. The initial presentation was categorized into motor versus cognitive based on carer report. Survival was calculated from initial symptom onset. Brain atrophy patterns on MRI were examined using a verified visual rating scale. In the ALS-FTD group, 39 were categorized as having an initial cognitive presentation, 16 had a motor presentation, which was associated with a much shorter survival of 33 months versus 63 months (p < .007). On cognitive testing there no differences found between motor versus cognitive ALS-FTD. When comparing ALS- FTD to bvFTD, ALS-FTD was characterized by reduced language (p < .001), verbal fluency (p = .001), naming (p = .007). and emotion processing (p = .01). ALS-FTD patients had more motor cortex atrophy than bvFTD patients, and those with a cognitive of ALS-FTD presentation had increased orbitofrontal atrophy compared to those with a motor presentation. Within the diagnosis of ALS-FTD those with an initial motor presentation have a much faster progression than those with a cognitive presentation, despite having similar cognitive changes, suggesting that disease progression in ALS-FTD may be related to non- cognitive factors including metabolic and physiological changes. These results provide possible markers to categorise patients into fast versus slow progressors, aiding in clinical trial development.